CN103189751A - Systems and methods for transfer of liquid samples - Google Patents
Systems and methods for transfer of liquid samples Download PDFInfo
- Publication number
- CN103189751A CN103189751A CN2011800421325A CN201180042132A CN103189751A CN 103189751 A CN103189751 A CN 103189751A CN 2011800421325 A CN2011800421325 A CN 2011800421325A CN 201180042132 A CN201180042132 A CN 201180042132A CN 103189751 A CN103189751 A CN 103189751A
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- Prior art keywords
- fluid distributor
- load system
- fluid
- axle
- sample array
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/56—Labware specially adapted for transferring fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0275—Interchangeable or disposable dispensing tips
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
- B01L3/0293—Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1011—Control of the position or alignment of the transfer device
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
- G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/16—Surface properties and coatings
- B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/103—General features of the devices using disposable tips
Abstract
A system for preparing biological sample contains a body including a proximal side and a distal side, a plurality of mandrels, a plurality of resilient elements, a plurality of fluid dispensers, and one or more samples. The mandrels are moveably positioned within the body, where each resilient element engages a respective one of the mandrels. Each of the fluid dispensers is configured to engage a distal end of a corresponding one of the mandrels. Each sample comprises a solution containing one or more nucleic acid sequences contained within at least one of the fluid dispensers.
Description
Technical field
The present invention relates to Load System and method by and large, such as being used in Load System and the method for source of supply to transfer liquid sample between the sample carrier.
Background technology
Microfluidic control relates to passes a kind of system or shift small volume of fluid between two or more position.For example, in biochemical field, need accurately control to be used for testing or measuring with preparation to the transfer in card, plate or the similar retainer member by chemical examination thing, reagent and/or bioactive fluid on a small quantity.
In recent years, the expectation that increases analyzable sample size during single test has caused the promotion for more and more littler sample volume.Under these circumstances, be transferred in sample panel or the card or the Fluid Volume on sample panel or the card can or be received the scope that rises at microlitre.
For example, developed the multi-through hole plate that is used for high flux screening, test and/or amplifying nucleic acid sequence or other biological sample, it keeps at least 3000 sample wells.Accurate and consistent filling between each sample well on single plate or a plurality of plate can help to provide result more accurately, and the result also allows at sample better contrast and the correlativity between each the measurement more accurately.
According to prior art, hope be in order to provide accurately, as one man to shift system, the apparatus and method that small amount of liquid is handled and tested.
Summary of the invention
Embodiments of the invention are directed to by and large in the source and be configured to receive improved device, the system and method that shifts small volume of fluid between the carrier of fluid.Embodiments of the invention are specially adapted to following such situation: what wherein need is at each experiment or tests a large amount of receiving vessel of about thousands of kinds of samples or the hole is come for carrying out gene sequencing, amplification program (for example, polymerase chain reaction (PCR), PCR in real time) etc.
Though embodiment disclosed herein and example are primarily aimed in biological chemistry and use, will recognize that embodiments of the invention also can apply in other application.For example, the present invention is applicable to the situation of wanting situation a small amount of and/or the accurately fluid of amount and/or needing or wish a large amount of sample volumes.
Each combination of two or more features in each feature disclosed herein and the such feature is included in the scope of the present invention, as long as the feature that is included in such combination is mutually not internally inconsistent.Additional aspect of the present invention, feature and advantage have been stated in description hereinafter and the claim, and have been not when considered in conjunction with the accompanying drawings that similar in the accompanying drawings part has similar Reference numeral.
Description of drawings
When read in conjunction with the accompanying drawings, from detailed description hereinafter, embodiments of the invention can be better understood.Such embodiment only is for example solution purpose, has described novelty of the present invention and unconspicuous aspect.Accompanying drawing comprises with figure below:
Fig. 1 is the skeleton view that is used for the system according to an embodiment of the invention of loading or transfer liquid sample.
Fig. 2 is for according to embodiments of the invention and be suitable for the figure of the sample array in the system shown in Fig. 1.
Fig. 3 is for according to embodiments of the invention and be suitable for the skeleton view of the fluid distributor in the system shown in Fig. 1.
Fig. 4 is the cross sectional view of the fluid distributor shown in Fig. 3.
Fig. 5 is the top perspective according to the transport subsystem of one embodiment of the invention.
Fig. 6 is the bottom perspective view of the transport subsystem shown in Fig. 5.
Fig. 7 is the top view of the transport subsystem shown in Fig. 5.
Fig. 8 is the cross-sectional perspective view of the transport subsystem shown in Fig. 5.
Fig. 9 is the sectional view of the inside of the transport subsystem shown in Fig. 5.
Figure 10 is the sectional view of the fluid distributor shown in Fig. 3 and Fig. 5 and fluid distributor axle far-end.
Figure 11 for the zoomed-in view of the axle near-end shown in Figure 10 and show according to one embodiment of the invention with the engaging of non-linear elastic element.
Figure 12 be the fluid distributor shown in Figure 10 with axle portion between the zoomed-in view that engages.
Figure 13 and Figure 14 are according to the partial view of two flexible members of one embodiment of the invention, show its operation.
Figure 15 shows the block diagram according to the method for one embodiment of the invention.
Figure 16 is according to the control of one embodiment of the invention and the synoptic diagram of disposal system.
Figure 17 is the zoomed-in view from the sample array platform of system shown in Fig. 1.
Embodiment
Referring to Fig. 1, show Load System 100 according to an embodiment of the invention.Load System 100 comprises housing 102, and during operation, housing 102 is being kept Load System 100 and is being in cleaning and controlled environment.Housing 102 comprises door, window or near entrance 105.As shown in fig. 1, door 105 can have open position (as shown in Figure 1) and off-position (not shown), and open position is used for providing towards the path of Load System 100, and off-position is used for providing controlled environment.
Referring to Fig. 2, system 100 comprises for various parts and subsystem in a plurality of vessel 108 that one or more fluids loaded or transfer to one or more sample array 110 exactly extraly.For example, system 100 can comprise sample array platform or supporting member 112, is used for that fixing and/or known position is kept or be fastened on to one or more sample array 110 and is handled by Load System 100 being used for.
Referring to Fig. 3 and Fig. 4, system 100 also comprises various stations, platform etc. for the treatment of group or the set of fluid distributor 115 extraly, and the group of fluid distributor 115 or set can be mounted be used to one or more fluids or the solution of transferring to sample array 110.For example, system 100 can comprise one or more fluid distributor retainers 118 and fluid distributor alignment station or plate 120 is set that fluid distributor retainer 118 is configured to be in the condition that is engaged by system 100 in order to keep fluid distributor 115 during operation.System 100 can comprise that also the fluid distributor that can be used to fill fluid divider 115 fills station, for example microtiter plate, planchet or sample panel 122, and be used for after using, receiving fluid distributor 115 throw aside storehouse 125.
Further with reference to figure 5 to Fig. 8, system 100 can comprise induction system 128, induction system 128 comprises head assembly 130, a plurality of axle 132, flexible member 134, stripper or mechanism for stripping 136.System 100 also can comprise steady arm 138, and steady arm 138 moves and locate this induction system 128 in housing 102.Head assembly 130 comprises framework 140 and head, plug-in unit or the block 142 that can be mounted or be attached on the framework 140, and head assembly 130 has proximal lateral 145 and distal side 148.In the illustrated embodiment, induction system 128 once keeps nearly 48 fluid distributors, and each fluid distributor 115 can be served the vessel 108 that are positioned at a subarea on the sample array 110.
In certain embodiments, this system 100 is for being used for carrying out the part of system greatly of biology/microorganism testing or processing.For example, system can comprise according to an embodiment of the invention: one or more sample array 110, and one or more biological samples or quilt chemical examination thing, this system 100 is used for sample or by the transfer of chemical examination thing, loads or deposit in one or more sample array; And/or test or disposal system, such as gene sequencing system or instrument or amplification system or instrument (for example, for the system or the instrument that use in conventional polymeric enzyme chain reaction (PCR), PCR in real time (qPCR), digital pcr (dPCR) and/or similar reaction).
For example, U.S. Patent No. 6,027,873 disclose a kind ofly for keeping the method for sample to analyze, and its equipment comprises the test board with a pair of opposed surface and a plurality of holes.In the hole each extends to the opposed surface another from one of opposed surface.Hole is arranged that in groups wherein each group has at least two row and two row holes.Group is arranged to set, and wherein each set has at least two row and two row groups.For analytic sample, at least one in the opposed surface of test board is immersed in the solution to be analyzed.The part of solution enters into the opening at each hole of the hole of the opposed surface that is submerged.In case hole has been filled solution, has then removed test board and test board and be maintained at the area supported top.Keep solution in surface tension each in hole.Analyze the solution in the one or more holes in these holes then, and identify solution in one of these holes to be used for further research.Mark is come according to its position in specific hole set and hole group in the position of identified solution.
U.S. Patent No. 6,387,331 disclose a kind of system and method for analyzing multiple fluid sample.This system has pressing plate, and this pressing plate has two substantially parallel plane surfaces and a plurality of through hole, and through hole is sized to make and by means of surface tension fluid sample is maintained in each through hole.Described through hole is shone in the optical radiation source, and optical arrangement has been analyzed the light of launching from through hole.Through hole can and can have less than 100 by individually addressing (addressable) receives the volume that rises.Can be by capillarity from the plane surface aspirated specimens, and according to embodiments of the invention, can distribute exactly, dilution and biased sample.
U.S. Patent No. 7,332,271 disclose equipment and the method that is used for carrying out with a kind of array format the long-pending chemistry of a plurality of while microbodys and biochemical reaction.In one embodiment, this form has comprised the micropore hole array in substrate.Except the oldered array as the sample chamber that allows to carry out a plurality of parallel reactions, array can be used for reagent storage and transfer, storehouse and shows that (library display), reagent are synthetic, combination, dilution and the desalination of a plurality of same reaction.Use the array facility optical analysis has been carried out in reaction, and allowed to carry out in real time optical analysis.External member can comprise the reaction part of micropore hole equipment and (multiple) method that will carry out in this equipment.
Sample array can be made by various known method.For example, sample array can be according to disclosed process in the U. S. application No. 20060105453 that announces, this application merges to herein in the mode that it quotes in full.U. S. application No. 20060105453 discloses the differently coated apparatus for the regulation reaction of carrying out a plurality of nano-volumes, this device comprises pressing plate, pressing plate has at least one outside surface that is modified to the regulation physicochemical property, a plurality of nano-volumes passages, each nano-volumes passage has at least one inside surface that is connected with at least one outside surface, at least one outside surface is optionally being applied randomly soluble smears, the smears is arrived at least one inside surface by physisorption, wherein, randomly soluble smears comprises the smears and is used for first component that a plurality of regulations are reacted.Also be provided for preparing and using the method for such device, and with respect to the align method of divider array position of microfluidic arrays.In divider array and the microfluidic arrays first can move with respect to framework, and this first another one is fixed with respect to framework in divider array and the microfluidic arrays.Determined from aligned position to the divider array with one of microfluidic arrays on the amount relevant with vector shift of fixed position.Thereby determined amount is used for the described divider array of guiding with respect to the location of microfluidic arrays.The sample array of U. S. application No. 20060105453 can be used in the system and method for the present invention.
Again referring to Fig. 2, illustrated in the sample array 110 of embodiment comprise a plurality of subareas or subarray 109, wherein each subarea 109 can comprise 4 * 4 arrays of small through hole 108.Alternatively, subarea 109 can comprise 5 * 5,6 * 6,8 * 8 or the array of higher quantity through hole 108.In certain embodiments, during handling sample, sample array 110 can be enclosed in coil neutralization/or two microslides between.In the illustrated embodiment, sample array 110 comprises individual subarea, 48 (4 * 12), and in 48 fluid distributors 115 each is configured in order to fill at least one subarea 109.
In certain embodiment, fluid distributor 115 comprises near-end endoporus 116 and far-end endoporus 117, and near-end endoporus 116 is characterised in that first axial length, and proximal openings has first internal diameter and is configured in order to receive the far-end of one of axle.The feature of far-end endoporus 117 can be that second axial length and distal openings have second internal diameter and be configured in order to receive at least a portion of sample.First diameter can be greater than 5 times of second diameters and between greater than 10 times of second diameters, for example, and in order to the favourable rigidity characteristic of the distal portion of fluid distributor 115 to be provided when fluid distributor 115 moves in sample array 110 surfaces.In certain embodiments, when being less than or equal to the minimum diameter of near-end endoporus 116, the maximum inner diameter of far-end endoporus 117 can provide favourable rigidity characteristic.In addition, when the ratio of first axial length and second axial length is from 0.8 to 1.2, can provide favourable rigidity characteristic.
In certain embodiments, the rigidity of having found to increase distal portion 117 provide bigger degree of accuracy and therefore in the through hole 108 of sample array 110 better fluids shift reliabilities.In these embodiments, contacting between the distal openings of distal portion 117 and sample array 110 surfaces is generally initial capillarity and the condition precedent that flows in the through hole 108 that enters into sample array 110.
Again referring to Fig. 1, the non-limiting example of the various elements of the used system 100 of transfering fluid between divider 118 and the sample array 110 will be described in greater detail in.In the illustrated embodiment, the mechanical organ of system 100 mainly is positioned at shell 102.When door 105 was closed, housing 102 helped the protection sample solution to avoid chip and pollution.Door 105 can comprise transparent material or window, and transparent material or window provide the pathways for vision to the automatic processing of one or more sample array.For example, door 105 can comprise glass or plastic material or window.In certain embodiments, can implement other control with the environment of further improvement in shell 102.For example, temperature controllable and humidity are to provide more favourable loading and test result.Can use humidity to control to reduce to be transferred to the fluid evaporator of sample array 110, thereby can realize being loaded fluid more than a sample array 110 at single robotization duration of test.
In the illustrated embodiment, sample array platform or supporting member 112 are used for keeping and one or more sample array 110 that align.Sample array platform 112 can keep one to four sample array 110.Referring to Figure 17, show the enlarged perspective of supporting member 112, wherein one of four available retainers have comprised sample array 110.
Fluid distributor alignment station or plate 120 is set is used in from fluid distributor retainer 118 initial acquisitions and improves described fluid distributor 115 about the aligning of the respective mandrels 132 of described induction system 128 after the fluid distributors 115.Especially, the variation of axial location that plate 120 can be used for reducing the top far away of each fluid distributor 115 is set.Can allow more uniform contact the between top far away and the sample array 110 by the precision that increases to some extent in the aligning that plate 120 provides is set, this more uniform contact has caused arriving more uniform sample loading in the sample array 110 then.In certain embodiments, plate 120 is set and comprises that a plurality of holes or hole are to receive corresponding fluid distributor 115.The spacing of hole or hole and size can be configured to when described top is inserted or is assembled in hole or the hole in order to the preset space length between the top that is provided at each fluid distributor retainer 118 and relative positioning.In this way, plate 120 is set and is provided at predetermined alignment tolerance between the top.In certain embodiments, the top of fluid distributor 115 is repeatedly rapped in the hole of divider 115 or hole or is vibrated to be provided at predetermined alignment tolerance between the top.
Station filled by fluid distributor or sample panel 122 has comprised (multiple) sample fluid for the treatment of to be received and finally be transported to by fluid distributor 115 (a plurality of) sample array 110.
Throwing aside storehouse 125 is configured to the fluid distributor that abandons 115 of being discharged by stripper 136 in order to receive.
According to embodiments of the invention, induction system 128 provides multiple function when other element of coupling system 100 uses.For example, induction system 128 can be used for filling one or more associated fluids to the set of fluid distributor 115, one or more fluids are transported to one or more sample array, and in case no longer need to abandon under the situation of set of fluid distributor 115 fluid distributor 115 set (for example, utilize comprising with previous used corresponding divider in the set of replacing some or all described fluid distributor 115 of the different fluid divider 115 of the identical or different fluid of the fluid that comprises).
Referring to Fig. 9 to Figure 11, now provide structure and the function of induction system 128 extraly.In the illustrated embodiment, the head assembly 130 of induction system 128 comprises framework 140, and framework 140 is configured to especially in order to supporting and/or location head 142.Head 142 comprises a plurality of cylindrical passage or through hole 150, and path or through hole 150 are configured to receive movably or slidably each in the axle 132.As finding out in Fig. 7, head 142 comprises the array of 4 * 12 through holes, perhaps has 48 through holes altogether to be used for receiving 48 different axles 132.According to particular system or functional requirement, the quantity of through hole 150 can be different.For example, head 142 can comprise few to one, two, three or four through holes 150 and receive axle 132.Alternatively, head 142 can comprise nearly 96,100,200 or more through hole 150 and reception axle 132.
In certain embodiments, each through hole 150 in head 142 is identical or substantially the same with the axle 132 that receives with all the other through holes 150 with the axle 132 that receives.Alternatively, one or more through holes 150 and/or the axle 132 that receives can be different with other through hole and/or axle, for example require in order to the difference that adapts to different sample array 110 or in the different piece or district of one or more sample array 110.For example, some in the axle can be configured in order to maintain the fluid distributor 115 more greater or lesser than other fluid distributor in the fluid distributor 115.
Can use various technology as known in the art or method to make head 142.For example, head 142 can form with die casting, and is machined out through hole 150 subsequently and places more accurately so that it to be provided.Alternatively, through hole 150 also can be poured into a mould with the remainder of head 142 and form.After cast, the other parts of through hole 150 and/or head 142 can be machined into (for example) in order to reference more accurately to be provided, and/or in order to the size that increases through hole 150 and/or they with respect to reference to or the precision of relative to each other position.
Axle 132 is configured in order to engage corresponding in the through hole 150 movably or slidably.The size of axle 132 and through hole 150 and/or tolerance can be defined as reducing the angle of each axle 132 or the amount of transfer movement when axle 132 passes across through hole 150.Lubricant optionally is used for increasing the freedom of motion of axle 132, for example, keeps more loose tolerance to allow being assembled to axle 132 in the through hole 150 more closely and/or to allow at the diameter of axle 132 and/or through hole 150.That in certain embodiments, can select the length of each through hole 150 and diameter recently provides axle 132 a certain amount of rotation or translation motion in through hole 150 in length and breadth.For example, in one embodiment, the length of each through hole 150 and the aspect ratio of diameter are between 6 to 1 and 7 to 1.Alternatively, the length of each through hole 150 and the aspect ratio of diameter can be 4 to 1 and 10 to 1 or between 4 to 1 and 10 to 1, perhaps can be 10 to 1 and 20 to 1 or between 10 to 1 and 20 to 1.
As shown in Figure 11, axle 132 can comprise counterbore 152, the diameter that counterbore 152 has is configured in order to receiving the part of flexible member 134, and/or its shoulder that has 155 is configured in order to rest position or the neutral position of axle 132 against block 142 proximal end faces to be provided.Axle 132 also can comprise through hole 158, and through hole 158 can have than the littler internal diameter of counterbore 152 internal diameters, for example, is configured in order to the ventilation of fluid distributor 115 to be provided during operation.Further referring to Figure 12, the shape that the top far away 160 of axle 132 can comprise is configured to engage close end or the endoporus 162 of fluid distributor 115.For example, top 160 far away can have taper, and this taper is configured in order to the taper in the near-end endoporus 162 of coupling and/or joint fluid distributor 115.In certain embodiments, the near-end endoporus can comprise one or more parts 165, and one or more parts 165 are configured in order to the gap between (a plurality of) the corresponding surface portion on (a plurality of) part 165 and top 160 far away to be provided.In certain embodiments, the surface on the top far away 160 of one or more axles 132 is configured in order to engage at two or more axial location 168 places that separate according to predetermined value or contact near-end endoporus 162.By making the axial distance between two axial locations 168 bigger relatively for the diameter of bore of near-end endoporus 162, found to improve the alignment accuracy between fluid distributor 115 and axle 132.Such alignment accuracy advantageously provides the higher precision that the top far away of fluid distributor 115 is positioned known position, for example during shifting sample between fluid distributor 115 and the sample array 110.
Also can use flexible member 134 to advantageously provide the higher precision that the top far away of fluid distributor 115 is positioned known position especially.Referring to Figure 11, flexible member 134 is configured in order to engage spindle 132 again, in order to apply power F for axle 132 on distal direction.Axle 132 is illustrated and is in idle or neutral position, and wherein shoulder 155 is pressed against on the head 142.Among the illustrated embodiment, flexible member 134 comprises base portion or substrate 170, first spring 172 and second spring 174 in Figure 11.In the illustrated embodiment, substrate 170 is coupled or be attached to the framework 140 of head assembly 130, and therefore fixes with respect to head assembly 130 and head 142.In the illustrated embodiment, reference planes 178 are positioned on the proximal end face of substrate 170; But it is a kind of like this plane that reference planes alternately are selected as: it is through the position that makes things convenient for above or below some other parts of head assembly 130 or the head assembly 130.
First spring 172 extends so that power F to be provided between the bottom of the counterbore 152 of substrate 170 and axle 132.Second spring, 174 to the first springs 172 are shorter, and bearing is in the bottom of counterbore 152.Now will discuss the use of second spring 174 hereinafter in more detail, should recognize that first spring 172 provides at power value F and between the nonlinear relationship between the distance between substrate 170 and the axle 132 with being used in combination of second spring 174.
Referring to Figure 13 and Figure 14, operation and the various advantage of flexible member 134 now disclosed.Figure 13 shows the structure A of system 100, and wherein, two axle 132A, 132B are coupled to corresponding flexible member 134A, 134B at one end, and are coupled to corresponding fluids divider 115A, 115B at other end place.When not contacting with the surface, the top far away of a plurality of fluid distributors 115 can realize constructing A.Alternatively, when only contacting with the proximal end face of sample array 110 slightly, only one in the top far away of a plurality of fluid distributors (fluid distributor 115A in this example) can realize constructing A.
As can be seen from Figure 13, the total length value of equaling Ζ on the far-end from single reference planes 178 to fluid distributor 115A or top
BCompare the total length value of the equaling Ζ from single plane 178 to fluid distributor 115B far-end or top
B-Δ
ZCan be by owing to the different slightly value of accumulating/piling up tolerance in each case to the difference in length of the far-end of 115A and 115B, wherein for the set of axle/ fluid distributor combination 115A, 132A and 115B, 132B, Z
BBe relatively large or maximum length, and Ζ
B-Δ
ZBe less relatively or minimum length.
In certain embodiments, advantageously, the top far away of two fluid distributor 115A, 115B is included in the common plane, and this common plane parallel is in the plane of passing through reference planes in Figure 13 at the z=0 place.For example, when fluid distributor 115A, 115B are used for zones of different transfering fluid to sample array 110, can need all divider tops contacting the top surface of sample array 110 simultaneously in order to guarantee from all divider transfering fluids.
Extraly referring to Figure 14, Load System 100 can be used to be structure B and advantageously realize this result by system 100 is placed as.As can finding out in the figure, by reducing head assembly 130, with greater than (but alternatively equaling) tolerance stack difference Δ
ZAmount z
1Reference planes 178 have been reduced.In this way, promote two axle 132A, 132B with respect to the proximal end face of head 142, thereby made the power that is produced by first spring 172 that is used for each flexible member 134A, 134B be transferred to the top far away of fluid distributor 115A, 115B.Therefore, as required, the top far away of fluid distributor 115A, 115B all contacts with the surface of sample array 110.Will appreciate that, in structure B since axle 132 from the head 142 proximal end face be shifted further, then the mean force on fluid distributor 115 increases.Therefore, with the variable in distance between the top far away of fluid distributor 115A, 115B from the value Δ
ZBe reduced to and equal zero or be substantially equal to zero value.Will appreciate that, in a similar manner, can make the top far away of fluid distributor 115A, 115B all contact the proximal end face of sample array 110, even on sample array 110 surfaces and incomplete when smooth.
Will appreciate that, above can expand to the fluid distributor 115 of bigger quantity about the given method of fluid distributor 115A, 115B, for example, 48 fluid distributors 115 of the induction system 128 shown in Fig. 5.In certain embodiments, selected length and the spring constant of first spring 172, thereby made and between all 48 tops far away of the fluid distributor 115 shown in Fig. 5 and sample array 110, produce relative constant power.As a supplement or as an alternative, can select length and the spring constant of first spring 172, thereby making that power between all or most of far away top of sample array 110 and fluid distributor 115 is fully low is lower than predetermined value on sample array 110 surfaces with the friction force between the tops far away.Found that such low-frictional force advantageously prevents or reduced the bending on top.Because the top bending that excessive friction causes can reduce to determine the degree of accuracy of apical position, this can weaken transfering fluid then unfriendly to the effect of vessel 108.
In certain embodiments, reduce at least 50% in reference planes 178 and more than the length variations between a plurality of top far away in two fluid distributors when the length variations that system is in structure when being in structure A than system 100 during B.In certain embodiments, when a plurality of fluid distributors 115 are in structure during A, the variable in distance of generation be from 5 microns to 5000 microns, and is in when constructing B this variable in distance less than 5 microns when a plurality of fluid distributors 115.
As finding out in Figure 11, Figure 13 and Figure 14, each in the flexible member 134 also can comprise second spring 174.At least one favourable purposes of second spring 174 be for head assembly 130 from the larger axis of the neutral position of the structure A shown in Figure 13 to displacement for, increase effective spring constant of flexible member 134.In certain embodiments, can use the increase of spring constant to come to produce bigger power at fluid distributor 115, for example, to help that accurately mutual aligning is aimed at and/or made it in the fluid distributor 115 each with reference coordinate.
In certain embodiments, flexible member 134 comprises element and second flexible member of first elastically deformable extraly or alternatively.Such element can for example comprise elastic foam and/or polymeric material, has the elastic modulus that is suitable for providing according to displacement characteristic predetermined force.The use of the replaceable or additional spring of such element (such as first spring 172 and second spring 174).In other embodiments, flexible member 134 comprises open loop or closure (closed close) electronic system, for example in order to the non-linear force according to the axle displacement characteristic to be provided.
In addition, stripper 136 comprises bias mechanism, bias mechanism comprises for example one or more biasing springs 186, biasing spring 186 is constructed stripper 136 bias voltages for being near-end, in the near-end structure, lower plate 182 be positioned at head assembly 130 places or near, come be used to being connected to fluid distributor 115 in order to expose the relatively large scope of axle 132.Stripper 136 also has the far-end structure, in the far-end structure, and more close far-end when the position of lower plate 182 and upper plate 180 is compared in the near-end structure.
In certain embodiments, when electromagnet is in when stopping using condition, stripper 136 is in the near-end structure, and wherein, stripper 136 can engage one or more fluid distributors 115, attached or be connected to one or more corresponding axles 132.In these embodiments, biasing spring 186 is being kept lower plate 182 and is being in proximal location.When starting electromagnet 188, make every effort to overcome the magnetic force of clothes on upper plate 180 and/or lower plate 182 by what biasing spring 186 produced, keep lower plate 182 thus and be the far-end structure, and remove or peeled off any fluid distributor 118 that is being engaged by corresponding axle 132 therefrom.
Will appreciate that stripper 136 alternately is configured to make when electromagnet is in entry condition stripper 136 kept and is the near-end structure, and when electromagnet 188 is in the condition of stopping using, be in far-end and construct.In addition, electromagnet 188 and/or upper plate 180 and/or lower plate 182 can be by some other power produce structure and replace.For example, electromagnet 188 can be replaced by the device of solenoid mechanism and/or hydraulic starting.
Referring to Figure 15, in certain embodiments, the method 300 that one or more samples are loaded in the sample array 110 comprises the key element 310 that head assembly 130, axle 132 and flexible member 134 are provided.Method 300 comprises extraly uses steady arm head assembly 130 to be moved to the key element 320 of fluid distributor retainer.Method 300 also comprises and is engaging the key element 330 of flexible member to produce first power.Method 300 also comprises to a plurality of axles and applies first power to engage the key element 340 that is placed in a plurality of fluid distributors 115 in the fluid distributor retainer movably.Method 300 also comprises and is engaging flexible member to produce the key element 350 of the second littler power than first power.Method 300 also comprises the key element 360 of second power that applies to a plurality of axles.Method 300 comprises key element 370 extraly, and wherein second power is enough to make all a plurality of fluid distributors 115 contacting sample array 110.
In key element 310, method 300 can merge the various embodiment of system 100 disclosed above.In non-limiting example, method 300 can be used in conjunction with the system as shown in Fig. 1, Fig. 8 and Figure 11.
Again referring to Fig. 1, key element 320 can comprise uses steady arm 138 to come moving-head assembly 130 to fluid distributor retainer 118 in order to engage any place from fluid distributor to 48 fluid distributor 115.In the key element 330 and 340 of method 300, use flexible member 134 to provide to make axle 132 to engage and aim at the required higher relatively power of fluid distributor 115.In the key element 350 and 360 of method 300, reuse flexible member 134 and produce sufficiently high power and be positioned to contact with the front surface of sample array 110 with the top far away with each fluid retainer 118.Simultaneously, the power that the top of fluid distributor 115 produces is enough low, thereby makes that top far away existence is seldom crooked or do not have bending.
At least in part because the nonlinear character of flexible member 134 is possible for this dynamic balance or the scope that provide accurate robotization to load necessary various tasks are provided.Thereby, during fluid is transferred to sample array 110, relatively low spring constant or elastic modulus provide the smooth required a large amount of axis that flatten of the small inequality for the top far away that makes fluid distributor 115 to move, but exist less relatively variation aspect the power that experiences on the top far away by each fluid distributor 115.Simultaneously, when axle travelled through preset distance, the spring constant of the increase that is provided by nonlinear characteristic or elastic modulus were enough high to avoid dropping to minimum point when attached or the aligning fluid distributor 118 during key element 330 and 340.
In the key element 370 of method 300, the top far away of each fluid distributor 115 strides across each surface portion or the subarea 109 of sample array 110 and moves.Owing to use lower strength that all tops far away of fluid distributor 115 are contacted with sample array 110, provide necessary capillarity to cause fluid flowing from all fluid distributors 115.
Further referring to Figure 16, the synoptic diagram of control system 400 comprises the system 100 shown in Fig. 1 and is used for the computing machine 410 of control system 100 between operation and alignment epoch.
Wherein the example of the system that can be analyzed the sample array that loads includes, but is not limited to case and thermal cycler/thermocycler (thermocycler).Exemplary case and thermal cycler are disclosed U.S. Patent No. 7,682,565 and the application No. 20060094108 that announces of the U.S. in, the mode that these documents quote in full with them and being integrated into herein.
For example, U.S. Patent No. 7,682,565 disclose a kind of at least one system to analyze for maintenance sample and reagent.This system comprises the coverture of pair of parallel, and wherein at least one is printing opacity, and this centering, the coverture of printing opacity forms the top, and another of this centering forms the bottom.Framework is placed between the coverture to limit internal volume with respect to coverture.Framework and coverture are associated with each other to form case, and case is impenetrable liquid basically.Microfluidic arrays is placed in the internal volume.This array comprises material sheet, and material sheet has a pair of opposed surface, certain thickness and passes a plurality of through holes that thickness extends between the surface, and through hole comprises at least one in sample and the reagent.
As another example, the application No. 20060094108 that the U.S. announces discloses the system that is used for making a plurality of sample thermal cycles.This system comprises case, and case has the fluid-tight chamber that is limiting internal volume.Microfluidic arrays is placed in the internal volume, and this array comprises material sheet, and material sheet has a pair of opposite surfaces, certain thickness and passes thickness between the surface and a plurality of through holes of extending.Thermal cycler with at least one hot controlled surface is suitable for and this case thermo-contact.
The description of the set execution optimal mode of expecting of the present invention is provided with comprehensive, clear, succinct and definite term above, and has made and use its process and mode, in order to make the relevant any technician in this area can make and use the present invention.But the present invention is easy to realize revising and is equal to the alternate configuration of above discussing fully.Therefore, the present invention's expection is not limited to disclosed specific embodiment.On the contrary, the present invention expection contain usually by following claim expressed belong to modification and alternate configuration in the spirit and scope of the present invention, claim is pointed out especially and is clearly advocated theme of the present invention.
Claims (79)
1. Load System comprises:
Main body comprises proximal lateral and distal side;
A plurality of axles of in described main body, locating movably;
A plurality of flexible members, each flexible member are engaging in the described axle corresponding one;
A plurality of fluid distributors, each fluid distributor are configured in order to engage the far-end of the corresponding axle in the described axle; And
Sample comprises in the described fluid distributor solution that comprises at least one, and described solution comprises one or more nucleotide sequences.
2. Load System according to claim 1, wherein, described main body comprises head and is placed in head insert in the described head that described axle is movably located in the described head insert.
3. Load System according to claim 2, wherein, described head comprises the proximal lateral that is placed in described head and a plurality of through holes between the distal side, each axle is positioned in the through hole corresponding in the described through hole movably.
4. Load System according to claim 1, wherein, each fluid distributor has near-end and far-end, each fluid distributor its proximal end by described a plurality of axles in the distal engagement of corresponding axle.
5. Load System according to claim 1, wherein, described flexible member is characterised in that, the nonlinear relationship between input parameter and the power that produced by described flexible member.
6. Load System according to claim 1, wherein, each fluid distributor has far-end, and described Load System is characterised in that the first distance set, the described first distance set comprises the distance of the far-end from single plane to each fluid distributor, and the described first distance set is characterised in that first minor increment and first ultimate range and described Load System are characterised in that first variable in distance equals described first ultimate range and deducts described first minor increment.
7. Load System according to claim 6, wherein, described Load System comprises:
First structure, wherein said Load System is characterised in that described first variable in distance; And
Second structure, wherein said Load System are characterised in that the second distance littler than described first variable in distance changes; And
Wherein said second distance variation equals second ultimate range and deducts second minor increment, described second ultimate range and second minor increment are characterised in that second distance set, and described second distance set comprises when described Load System and is in described second distance from described single plane to each fluid distributor far-end when constructing.
8. Load System according to claim 7, wherein, described second distance changes and is less than or equal to 50% of described first variable in distance.
9. Load System according to claim 7, wherein, described first variable in distance is from 5 microns to 5000 microns, and described second distance changes less than 5 microns.
10. Load System according to claim 7, also comprise: sample array, comprise a plurality of vessel, each vessel is configured to receive sample in order at least one fluid distributor from described fluid distributor, and wherein the far-end that is in described second all fluid distributors when constructing when described Load System is contacting described sample array.
11. Load System according to claim 7, wherein, each in the described axle has shoulder, and described first structure is characterised in that all shoulders are contacting described main body.
12. Load System according to claim 11, wherein, described Load System comprises the 3rd structure, wherein, described Load System is characterised in that the 3rd distance set, described the 3rd distance set comprises the distance from single plane to each fluid distributor far-end when described Load System is in described the 3rd structure, and described the 3rd distance set has the mean value that whole three distances littler than the mean value of whole second distances set are gathered.
13. Load System according to claim 12, wherein, described second structure is characterised in that first mean force between described axle and described fluid distributor, and described the 3rd structure is characterised in that the second littler mean force of described first mean force of ratio between described axle and described fluid distributor.
14. Load System according to claim 1 also comprises: sample array comprises a plurality of vessel that are configured to receive in order at least one fluid distributor from described fluid distributor sample.
15. Load System according to claim 14, wherein, described sample array comprises plate, and described a plurality of vessel comprise a plurality of through holes of settling to the rear side of described sample array from the front side of described sample array, described plate comprises top surface and basal surface, described top surface and basal surface comprise hydrophobic material separately, and described plate also comprises the hydrophilic material between the surface that is placed in described plate.
16. Load System according to claim 15, wherein, the described through hole of described sample array is characterised in that, the diameter of at least one is from 10 microns to 600 microns in described front side and the rear side.
17. Load System according to claim 16, wherein, the described through hole of described sample array is characterised in that, the diameter of at least one in described front side and the rear side is from 300 microns to 340 microns.
18. Load System according to claim 1, wherein, described flexible member comprises the element of first elastically deformable and the element of second elastically deformable, and described system is characterised in that:
First the structure, wherein, the element of described first elastically deformable between described main body and described axle by compression, and the element of described second elastically deformable between described main body and described axle not by compression; And
Second the structure, wherein, the element of the element of described first elastically deformable and second elastically deformable between described main body and described axle all by compression.
19. Load System according to claim 18, wherein, the material of described first elastically deformable has first elastic modulus, and the material of described second elastically deformable has second elastic modulus that is different from described first elastic modulus.
20. Load System according to claim 1, wherein, described flexible member comprises a plurality of springs, second end of corresponding axle during each spring has first end that engaging base portion and engaging described axle.
21. Load System according to claim 20, wherein, described base portion is the substrate that is attached on the proximal lateral of described main body, and first termination of each spring is being closed described substrate.
22. Load System according to claim 1, wherein, described flexible member comprises more than first spring and more than second spring.
23. Load System according to claim 22, wherein, each spring in described more than first spring has first end that is engaging described main body and second end that is engaging one of described a plurality of axles, and each spring in described more than second spring has first end that is engaging described main body and second end that is engaging one of described a plurality of axles.
24. Load System according to claim 22, wherein, each spring in described more than second spring is placed in the corresponding spring in described more than first spring.
25. Load System according to claim 22, wherein, each spring that each spring in described more than first spring has in first spring constant and described more than second spring has second spring constant.
26. Load System according to claim 25, wherein, described second spring constant is higher than described first spring constant 10% to 500%.
27. Load System according to claim 22, wherein, each spring in described more than first spring has first length, and each spring in described more than second spring has second length.
28. Load System according to claim 27, wherein, described first length is longer than described second length at least 10% to 500%.
29. Load System according to claim 1, also comprise: stripper, wherein each fluid distributor has near-end and far-end, described Load System has in its proximal end by a plurality of fluid distributors that corresponding axle was engaging in described a plurality of axles, and each stripper is configured in order to described a plurality of fluid distributors are separated with described a plurality of axles.
30. Load System according to claim 29, wherein, described system is characterised in that first structure and second structure, and at described first structure, described fluid distributor is engaged by described a plurality of axles; At described second structure, described stripper stops described fluid distributor to join the far-end of described axle to.
31. Load System according to claim 30, wherein, described stripper is included in the lower plate of settling from described main body on the distal direction.
32. Load System according to claim 31, wherein, described lower plate comprises a plurality of through holes, and each axle is positioned at one of described a plurality of through holes of described lower plate.
33. Load System according to claim 31 also comprises: force generating apparatus is configured to be in described second structure in order to keep described system.
34. Load System according to claim 33, wherein, described force generating apparatus is electromagnet.
35. Load System according to claim 34, wherein, described electromagnet has entry condition and entry condition not, and when described electromagnet was in described not entry condition, described system held was in described first structure; When described electromagnet was in described entry condition, described system held was in described second structure.
36. Load System according to claim 33, wherein, described stripper comprises the upper plate that is attached to described lower plate.
37. Load System according to claim 33, wherein, described stripper comprises the bias voltage flexible member, and described bias voltage flexible member produces biasing force, and described biasing force is configured to be in described first structure in order to keep described system.
38. according to the described Load System of claim 37, wherein, described bias voltage flexible member comprises at least one spring, described at least one spring has first end that is attached to described stripper and second end that is attached to described main body.
39. according to the described Load System of claim 37, wherein, described force generating apparatus has entry condition, described entry condition produces the driving force bigger than the biasing force of described bias voltage flexible member, and described system held is in described second structure thus.
40. according to the described Load System of claim 37, also comprise: fluid distributor retainer and limited part, described fluid distributor forms first group of fluid distributor, and described fluid distributor retainer comprises second group of fluid distributor, second group of fluid distributor is described first group subclass, and described limited part has limited some fluid distributor at least in described second group of fluid distributor.
41. according to the described Load System of claim 40, wherein, described limited part comprises from a plurality of finger pieces of the distal surface projection of described stripper and comprises the distal portion that is placed between described distal surface and the described second group of restricted fluid distributor.
42. Load System according to claim 1, wherein, each fluid distributor comprises at least one inside surface, its through being subject to processing in order to make described at least one inside surface possess hydrophilic property more.
43. Load System according to claim 1, wherein, each fluid distributor comprises at least one inside surface, and described at least one inside surface stands Cement Composite Treated by Plasma in order to make described at least one inside surface possess hydrophilic property more.
44. Load System according to claim 1, wherein, each fluid distributor comprises far-end, and far-end comprises that diameter is from 100 microns to 2000 microns opening.
45. Load System according to claim 1, wherein, each fluid distributor comprises far-end, and far-end comprises that diameter is from 450 microns to 550 microns opening.
46. Load System according to claim 1, wherein, each fluid distributor comprises near-end endoporus and far-end endoporus, and described near-end endoporus is characterised in that first axial length, and proximal openings has first internal diameter and is configured in order to receive the far-end of one of described axle; Described far-end endoporus is characterised in that second axial length, and distal openings tool second internal diameter and being configured in order to receive at least a portion of sample.
47. according to the described Load System of claim 46, wherein, described first internal diameter is greater than 5 times of described second internal diameters and between greater than 10 times of described second internal diameters.
48. according to the described Load System of claim 46, wherein, the maximum inner diameter of described far-end endoporus is less than or equal to the minimum diameter of described near-end endoporus.
49. according to the described Load System of claim 46, wherein, described first axial length is from 0.8 to 1.2 with the ratio of described second axial length.
50. Load System according to claim 1 also comprises: steady arm is attached on the described main body and is configured in order to mobile described main body in described Load System.
51. according to the described Load System of claim 50, also comprise one or more in following:
Sample array has a plurality of vessel, and described a plurality of vessel are configured in order to receive described sample;
The sample array platform is configured in order to keep described sample array in the fixed position;
The fluid distributor retainer is configured to be in the condition that is engaged by described a plurality of axles in order to keep described a plurality of fluid distributor;
Fluid distributor alignment station;
Fluid distributor is filled station;
Throw aside the storehouse, be used for reception fluid distributor when described fluid distributor breaks away from one or more axle of described a plurality of axles; And
Housing is used at least part of of the described Load System of sealing.
52. according to the described Load System of claim 51, also comprise two or more in following:
A plurality of sample array have a plurality of vessel, and a plurality of vessel are configured in order to receive described sample;
A plurality of sample array platforms are configured to be in a fixed position in order to keep described one or more sample array;
A plurality of fluid distributor retainers are configured to be in the condition that is engaged by described a plurality of axles in order to keep described a plurality of fluid distributor;
A plurality of fluid distributor alignment stations;
A plurality of fluid distributors are filled station;
A plurality of storehouses of throwing aside are used for receiving fluid distributor when described fluid distributor breaks away from one or more axle of described a plurality of axles; And
A plurality of housings are used at least part of of the described Load System of sealing.
53. according to the described Load System of claim 51, also comprise: controller is configured in order to by controlling the described main body that described steady arm moves described Load System.
54. according to the described Load System of claim 53, wherein, described controller comprises one or more algorithms, described algorithm configuration becomes in order to control described Load System so that two or more functions in the following function to be provided:
Described main body is moved to described fluid distributor retainer;
Described a plurality of fluid distributor is engaged with described a plurality of axles;
Described a plurality of fluid distributors are positioned described sample array top;
Make described a plurality of fluid distributor be adjacent to described fluid distributor and fill the station location;
Reducing described a plurality of fluid distributor contacts with described sample array up to all fluid distributors;
Move described a plurality of fluid distributor along the surface of described sample array, so that the interior one or more samples of one or more fluid distributors that will be contained in described a plurality of fluid distributor are transferred in described a plurality of vessel of described sample array;
Raise described a plurality of fluid distributor away from described sample array;
Described a plurality of fluid distributors are moved to the described top, storehouse of throwing aside from described sample array top;
Described a plurality of fluid distributor and described a plurality of axle are broken away from, in order to described a plurality of fluid distributors are deposited to described throwing aside in the storehouse.
55. according to the described Load System of claim 54, wherein, described controller comprises computing machine, and described one or more algorithm is arranged in computer-readable storer.
56. a Load System comprises:
Main body comprises proximal lateral and distal side;
A plurality of axles of in described main body, locating movably;
A plurality of flexible members, each flexible member are engaging a corresponding axle in the described axle;
A plurality of fluid distributors, each fluid distributor are configured in order to engage the far-end of corresponding in a described axle axle; And
A plurality of samples, each sample comprises different solutions, described different solutions comprises the various combination of one or more nucleotide sequences;
In the wherein said sample each is contained in in described a plurality of fluid distributor at least one.
57. one kind is loaded into method in the sample array with sample, comprising:
The provider, place a plurality of axles and non-linear elastic element in the described main body;
Use steady arm, described main body is moved to the fluid distributor retainer;
Engage described flexible member to produce first power;
Apply described first power to described a plurality of axles and place a plurality of fluid distributors in the described fluid distributor retainer with joint;
Engage described flexible member to produce second power less than described first power; And
Apply described second power to described a plurality of axles;
Wherein said first power is enough to make described a plurality of fluid distributor contacting sample array.
58. according to the described method of claim 57, it also comprises:
Move described a plurality of fluid distributor along the surface of described sample array; And
Transfer in one or more vessel of described sample array being contained in described a plurality of fluid distributor the one or more samples in the one or more fluid distributors.
59. according to the described method of claim 57, it also comprises:
Make described a plurality of fluid distributor break away from described sample array; And
Make described a plurality of fluid distributor break away from described a plurality of axle.
60. according to the described method of claim 59, it also comprises:
Described a plurality of fluid distributors are moved to throw aside the storehouse; And
Described a plurality of fluid distributors are deposited to the described storehouse of throwing aside.
61. according to the described method of claim 57, it also comprises:
The fluid distributor that engages is moved to fluid distributor alignment station; And
Adjust in the described fluid distributor aligning of at least one.
62. according to the described method of claim 57, it also comprises:
Described a plurality of fluid distributors are moved to fluid distributor fill station; And
One or more fillings in the described divider comprise the solution of one or more nucleotide sequences.
63. according to the described method of claim 57, it also comprises: control described sample array environment on every side.
64. according to the described method of claim 63, it is characterized in that, control described environment and comprise the humidity of keeping around the described sample array.
65. according to the described method of claim 57, it also comprises:
Sampling array platform, the sample array platform configuration becomes to be in a fixed position in order to keep described sample array; And
Use at least one calibration clamp to calibrate described steady arm.
66. according to the described method of claim 65, it also comprises:
Using before described at least one calibration clamp calibrates described system, utilizing described at least one calibration clamp to replace one or more in described sample array and the described sample array platform; And
Using after at least one calibration clamp calibrates described system, making one or more in described sample array and the described sample array platform turn back to described Load System.
67. Load System according to claim 1, wherein, described a plurality of axles slidably are positioned in the described main body at least in part.
68. Load System according to claim 1, wherein, each fluid distributor is configured in order to engage the far-end of corresponding axle in the described axle slidably.
69. Load System according to claim 1 also comprises: a plurality of sample array, each sample array comprises a plurality of vessel, described a plurality of vessel are configured to receive sample in order at least one fluid distributor from described fluid distributor.
70. Load System according to claim 1 also comprises: four sample array, each sample array comprises a plurality of vessel, described a plurality of vessel are configured at least one fluid distributor reception sample from described fluid distributor.
71. a Load System comprises:
Main body;
A plurality of axles, each axle are positioned in the described main body at least in part movably;
At least one flexible member is engaging at least one axle in described a plurality of axle;
A plurality of fluid distributors, each fluid distributor in described a plurality of fluid distributors has near-end, and described near-end is configured in order to engage the far-end of corresponding axle in described a plurality of axle movably; And
Plate comprises through hole,
Wherein said fluid distributor is configured to comprise in order to contact the described plate of through hole, and transports fluid at least one through hole in the described through hole.
72. a Load System comprises:
Main body;
A plurality of axles, each axle are positioned in the described main body at least in part movably;
A plurality of flexible members, each flexible member in the described flexible member is engaging one of described a plurality of axles, and each flexible member comprises a plurality of springs, and described a plurality of springs are attached between the corresponding axle in described main body and the described a plurality of axles; And
A plurality of fluid distributors, each in described a plurality of fluid distributors has near-end, and described near-end is configured in order to engage the far-end of corresponding axle in described a plurality of axle movably.
73. a Load System comprises:
Main body;
A plurality of axles, each axle are movably located in the described head at least in part;
At least one flexible member is engaging at least one in described a plurality of axle;
A plurality of fluid distributors, each in described a plurality of fluid distributors has near-end, and described near-end is configured in order to engage the far-end of corresponding axle in described a plurality of axle movably; And
Stripper comprises plate, and described plate is configured in order to described a plurality of fluid distributors and described a plurality of axle are peeled off.
74. a Load System comprises:
Movably main body engages movably with a plurality of axles;
Sample array has a plurality of vessel, and described a plurality of vessel are configured in order to receive sample;
The sample array platform is configured to be in a fixed position in order to keep described sample array;
The fluid distributor retainer is configured to be in the condition that is engaged by described a plurality of axles in order to keep described a plurality of fluid distributor;
Fluid distributor alignment station;
Fluid distributor is filled station;
Throw aside the storehouse, reception fluid distributor when being used for the one or more axles disengaging when described fluid distributor and described a plurality of axles; And
Housing is used at least part of of the described Load System of sealing.
75. a fluid distributor comprises:
At least one inside surface, described inside surface through being subject to processing in order to make described at least one inside surface possess hydrophilic property more;
Far-end, far-end comprise that diameter is from 100 microns to 2000 microns opening; And
Near-end endoporus and far-end endoporus, described far-end endoporus is characterised in that first axial length and distal openings have first internal diameter and be configured in order to receive the far-end of one of described axle, described near-end endoporus is characterised in that second axial length and proximal openings have second internal diameter and be configured in order to receive at least a portion of described sample, wherein:
Described first internal diameter is greater than 5 times of described second internal diameters and between greater than 10 times of described second internal diameters,
The maximum inner diameter of described far-end endoporus is more than or equal to the minimum diameter of described near-end endoporus, and
Described first axial length is from 0.8 to 1.2 with the ratio of described second axial length.
76. one kind is loaded into method in the sample array with sample, comprising:
The main body that will comprise axle moves to the fluid distributor retainer;
Apply first power to engage a plurality of fluid distributors that place in the described fluid distributor retainer movably to described a plurality of axles;
Described main body is moved to fluid fill station;
Fill one or more fluid samples to described fluid distributor;
Described main body is moved to the sample array station;
Apply second power less than described first power so that described a plurality of fluid distributor is contacting sample array to described a plurality of axles;
Move described a plurality of fluid distributor along the surface of described sample array;
One or more samples in the one or more fluid distributors that are contained in described a plurality of fluid distributor are transferred in one or more vessel of described sample array.
77. according to the described method of claim 76, it also comprises:
Described a plurality of fluid distributor and described sample array are broken away from; And
Described a plurality of fluid distributor and described a plurality of axle are broken away from.
78. according to the described method of claim 76, it also comprises:
Described a plurality of fluid distributors are moved to throw aside the storehouse; And
Described a plurality of fluid distributors are deposited to described throwing aside in the storehouse.
79. according to the described method of claim 76, it also comprises:
The a plurality of flexible members that engage are moved to fluid distributor alignment station; And
Adjust in the described fluid distributor aligning of at least one.
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| CN109313434A (en) * | 2016-06-09 | 2019-02-05 | 豪夫迈·罗氏有限公司 | The method of laboratory sample distribution system and operation laboratory sample distribution system |
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Also Published As
| Publication number | Publication date |
|---|---|
| US20140017148A1 (en) | 2014-01-16 |
| US20110318241A1 (en) | 2011-12-29 |
| US20170182496A1 (en) | 2017-06-29 |
| US10821444B2 (en) | 2020-11-03 |
| CN103189751B (en) | 2016-08-31 |
| WO2012006084A2 (en) | 2012-01-12 |
| CN106443039A (en) | 2017-02-22 |
| EP2585834B1 (en) | 2017-12-20 |
| CN106443039B (en) | 2018-04-24 |
| EP2585834A2 (en) | 2013-05-01 |
| WO2012006084A3 (en) | 2012-05-10 |
| US8529848B2 (en) | 2013-09-10 |
| US9604218B2 (en) | 2017-03-28 |
| EP2585834A4 (en) | 2016-04-13 |
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